The molecular mechanism(s) by which steroid hormones regulate the release of hypothalamic releasing hormones and thereby control the release of pituitary hormones is not well defined. At least three loci for steroid hormone action have been identified: extrahypothalamic brain nuclei, the hypothalamus and the pituitary. Depending on the species under study, the secretion of gonadotropins by the pituitary is to a greater or lessor extent controlled by neurally-mediated environmental influences (including endogenous steroids acting on the brain). Our laboratory has shown that specific estrogen receptors exist in discrete regions of the brain and that the occupation of these by estrogen and their subsequent translocation to the nucleus results in the activation of RNA polymerase II and subsequent alterations in the subcellular content, packaging and release of luteinizing hormone releasing hormone (LHRH) in the hypothalamus. We propose to examine the molecular mechanisms by which steroids control the activity of neural and neurosecretory elements of the central nervous system (CNS). The interaction of steroids with receptors in the CNS will be investigated with respect to subsequent: activation of endogenous nuclear RNA polymerases; modulation of protein synthesis and processing, neurotransmitter receptors, transport systems and biosynthetic enzymes; regulation of the subcellular distribution, degradation and release of neuropeptides. Using embryonic, neonatal and adult tissues, these studies should afford a description at the molecular level of those events involved in the development and adult functioning of the hypothalamic hypophyseal axis.